Department of Biology, Masaryk University, 62500 Brno, Czech Republic.
International Clinical Research Center, St. Anne's University Hospital in Brno, 62500 Brno, Czech Republic.
Nucleic Acids Res. 2020 Jan 24;48(2):694-708. doi: 10.1093/nar/gkz1052.
The proper repair of deleterious DNA lesions such as double strand breaks prevents genomic instability and carcinogenesis. In yeast, the Rad52 protein mediates DSB repair via homologous recombination. In mammalian cells, despite the presence of the RAD52 protein, the tumour suppressor protein BRCA2 acts as the predominant mediator during homologous recombination. For decades, it has been believed that the RAD52 protein played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (SSA). Recent studies have identified several new functions of the RAD52 protein and have drawn attention to its important role in genome maintenance. Here, we show that RAD52 activities are enhanced by interacting with a small and highly acidic protein called DSS1. Binding of DSS1 to RAD52 changes the RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates SSA activity and promotes strand invasion. Our work introduces for the first time RAD52 as another interacting partner of DSS1 and shows that both proteins are important players in the SSA and BIR pathways of DSB repair.
正确修复有害的 DNA 损伤，如双链断裂，可以防止基因组不稳定和致癌作用。在酵母中，Rad52 蛋白通过同源重组介导 DSB 修复。在哺乳动物细胞中，尽管存在 RAD52 蛋白，但肿瘤抑制蛋白 BRCA2 在同源重组过程中充当主要的介导物。几十年来，人们一直认为 RAD52 蛋白在 DSB 修复中仅起着易错的单链退火（SSA）的备用作用。最近的研究已经确定了 RAD52 蛋白的几个新功能，并引起了人们对其在基因组维护中的重要作用的关注。在这里，我们表明 RAD52 的活性通过与一种称为 DSS1 的小而高度酸性的蛋白质相互作用而增强。DSS1 与 RAD52 的结合改变了 RAD52 的寡聚构象，调节了其 DNA 结合特性，刺激了 SSA 活性并促进了链入侵。我们的工作首次将 RAD52 作为 DSS1 的另一个相互作用伙伴，并表明这两种蛋白质都是 DSB 修复的 SSA 和 BIR 途径中的重要参与者。
